Advances in Alzheimer's Disease

Clinical Review Advances in Alzheimer’s Disease A Review for the Family Physician Man? Elizabeth Roth, M l), MSA Southfield, Michigan Alzheimer’s disease accounts for approximately two disease involves a two-pronged approach: behavioral- thirds of all cases o f dementia in the United States and supportive care and pharmacologic control o f disrup S90 billion in health care costs annually. Clinical and tive behavioral symptoms. In the future, drug therapy laboratory diagnostic tools have been refined so that may be available to maintain memory and cognitive clinicians now can diagnose Alzheimer’s disease with function. Cholinesterase inhibitors, which block the de up to 90% accuracy. Criteria for clinical diagnosis have crease in choline acetvltransferasc activity associated been outlined by a work group o f the National Insti with Alzheimer’s disease, appear promising. The realis tute of Neurological and Communicative Disorders tic goal of health care providers at the present time, and Stroke and the Alzheimer’s Disease and Related however, should be symptom control rather than dis Disorders Association. Key diagnostic tools include a ease reversal. complete patient history', mental status testing, and a thorough diagnostic workup to exclude the possibility' Key words. Alzheimer’s disease; dementia; patient care- of a reversible disease mimicking the symptoms of Alz planning; cholinesterase inhibitors. (/ ham Pract 1993; heimer’s disease. Currently, management of Alzheimer’s 37:593-607) Alzheimer’s disease is one o f the most ironic and tragic among unaffected subjects of the same age, and it has consequences o f modern medicine’s success in prolong been suggested that the disease has become the third or ing survival until the 7th, 8th, and even 9th decade ot fourth ranking cause of death (usually resulting from life. Family physicians can expect to encounter this re pneumonia)2 among people between the ages of 75 and lentless and debilitating disorder in an estimated 1 of 85 vears.3 Alzheimer’s disease has now emerged as the leading 1000 patients aged 60 to 65 years of age, in 4 of 100 cause of dementia before and after age 65 years, account patients over 65 years o f age, and in as many as half ot ing for two thirds of all cases o f dementia. As such, its patients over 85 years of age.1 public health impact is enormous. Alzheimer’s disease In personal terms, Alzheimer’s disease spells devas affects approximately 4 million people and is the most tation for patient and family. Its course is characterized common reason for admitting someone to a nursing by worsening memory loss and personality changes home in the United States.3-5 According to one widely (sometimes including psychotic behavior), progressing cited analysis performed in 1987, the annual costs for a to global confusion, and ultimately, to complete cogni family to care for a patient with Alzheimer’s disease- tive disintegration. The death rate among patients with amount to over $18,0006; the annual bill for the nation Alzheimer’s disease is two to four times greater than that as a whole has now reached $90 billion.4 As the US population ages, the financial and human toll o f Alzhei Submitted, revised, August 5, 1993. mer’s disease will continue to increase. Many clinicians regard the diagnosis and manage From the Department o f Family Practice and the Geriatric Programs, Providence Medical Centers, Southfield, Michigan. Requests for reprints should he addressed to ment o f dementia with frustration, if not fatalism. Such Maty Elizabeth Roth, M D, Chairman, Department of Family Practice, 222, ( an attitude, however, is unwarranted. First, dementia Pmndencc Drive, Southfield, M I 48075. © 1993 Appleton 8c Lange ISSN 0094-3509 593 The Journal of Family Practice, Vol. 37, No. 6, 1993 Alzheimer’s Disease may stem from any o f a number of medically or surgically Table 1. Brain Changes in Alzheimer’s-Tvpe Dementia correctable conditions unrelated to Alzheimer’s disease. Compared With Normal Aging Process Since the cognitive impairment associated with these Alzheimer’s-Type Dementia Normal Aging conditions is only reversible if identified and treated • Senile plaques throughout the • Senile plaques absent or early,7 a thorough diagnostic workup is always required general cortex scanty in patients with suspected Alzheimer’s disease. Second, although there is still no pharmacologic “quick fix” for • Large numbers o f neurofibrillar)' • Neurofibrillar)' tangles absent tangles in medial temporal Alzheimer’s disease, recent research has sparked the de or scant)'; if present, usuallv structures, including the confined to the hippocampus velopment of promising new drugs that may help reverse hippocampus; also frequently or slow memory loss and cognitive impairment. Alzhei present in the general cortex mer’s disease is one of several currently irreversible de • Granulovacuolar degeneration • Much less frequent mentias and requires precise diagnosis. As with many and Hirano bodies in other chronic disorders of older patients, reasonable ther hippocampus frequent apeutic goals are improvement, control, or slowing of • Severe cholinergic deficit present • Absent progression, rather than cure. Newly available therapies, including behavioral, environmental, and pharmacologic • Marked reduction of brain • 7 % - 10% reduction of brain weight: brains from patients weight by the 9th decade approaches, may permit a more active and optimistic with Alzheimer’s-type dementia approach to the management o f Alzheimer’s disease. weigh ± 10% —15% less than New therapies may even alter the clinical course of Alz those from age-matched nondemented persons heimer’s disease if the disorder can be diagnosed and N ote: The important feature is that the brain changes in Alzheimer’s-type dementia treated early. appear in combination and profusion. This review provides a summary of the most current Reprinted with permission from Van der Cammcn TJM. Diagnostic approaches and management aspects o f early dementia. Delft, Netherlands: Eburon Publishers, 1991. research regarding the causes, diagnosis, and manage ment o f the disease, and potential therapies that may be used to treat Alzheimer’s disease. more typical changes found in Alzheimer’s-type dementia contrast with changes observed during the normal aging process (Table 1). What Causes Alzheimer’s Disease? Neurochemical Alterations Histopathologic Features A good correlation exists between the histopathological It was 85 years ago that Alois Alzheimer first published changes, neurochemical abnormalities, and some cogni his classic description o f cerebral cortical changes in a tive and memory deficits found in patients with Alzhei middle-aged woman who had died with progressive de mer’s disease. For example, loss o f neurons from the basal mentia. Alzheimer’s findings are still the defining patho nucleus of Meynert has been associated with a concom logic features o f the disease that now bears his name. itant decrease in cholinergic function, and this decrease in Changes found in all patients with Alzheimer’s dis cholinergic function has been linked to memory dysfunc ease include neurofibrillary tangles (tangles of fibers); tion. neuritic plaques (clusters of degenerating nerve endings); The above relationship, termed the cholinergic hypoth widespread, nonuniform atrophy o f the brain; and loss o f esis o f memory dysfunction, theorizes that changes in predominately large neurons and synapses.5 Cell loss, cholinergic activity occur in the brains o f patients with plaques, and tangles regularly occur in the neocortex dementia, and that these changes play an important role (especially the association areas) and the hippocampus. in contributing to the memory loss and cognitive prob Loss of cholinergic neurons from the basal nucleus of lems seen in patients with Alzheimer’s disease. Thus, it Mcyncrt is a common finding. A less common finding is follows that improvement of cholinergic function by the loss of serotonergic neurons from the dorsal segmen drugs that enhance cholinergic transmission should also tal nuclei, and noradrenergic neurons from the locus improve some of the symptoms of dementia. The evi serialize.8 Conversely, the primary motor, somatosen dence in support o f a cholinergic involvement in Alzhei sory, and visual cornices tend to be spared.1 In addition, mer’s disease follows. the brains of patients with Alzheimer’s disease weigh Choline acctyltransferase (CAT) is the enzyme re some 10% to 15% less than those of age-matched con sponsible for the formation of the ncurotransmittcr ace trols. There is some overlap, however, since with normal tylcholine. Autopsy analysis o f the brains o f patients with aging the brain atrophies and decreases in weight.5 The Alzheimer’s disease show a 40% to 90% reduction in 594 The Journal of Family Practice, Vol. 37, No. 6, 1993 Alzheimer’s Disease Roth CAT activity in the cerebral cortex and hippocampus,5 reduction in cortical somatostatin.12 Still to be deter brain areas traditionally associated with learning. This mined is whether changes in these neurotransmitter sys decrease in CAT activity is considered one of the chief tems contribute to cognitive impairment and how.11 biochemical hallmarks o f Alzheimer’s disease and corre The presence of neurofibrillary tangles and neuritic lates well with the degeneration o f neurons originating in plaques consisting of a core of excess /3-amvloid peptide the basal nucleus o f Meynert and projecting into the (28 to 43

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